A novel function of RING finger protein 10 in transcriptional regulation of the myelin-associated glycoprotein gene and myelin formation in Schwann cells.
Myelin-associated glycoprotein (MAG) has been detected in Schwann cells prior to the onset of myelination, suggesting its functions in the initiation of myelination. However, transcriptional regulatory mechanisms of MAG remain to be elucidated. Here, we analyzed the promoter of the MAG gene by using luciferase reporter systems in the primary rat Schwann cells. We identified a novel cis-acting element located 160 bp upstream from the MAG transcription initiation site. Using the identified cis-element as a bait, we performed yeast one-hybrid screening and isolated a cDNA encoding a RNF10 as a putative trans-acting protein. When overexpressed in Schwann cells, RNF10 enhanced the activity of the MAG promoter. When RNF10 expression in Schwann cells was knocked down by siRNA, endogenous MAG mRNA and protein expression decreased. Furthermore, we evaluated myelin synthesis using Schwann cell-DRG neuron cocultures. When Schwann cells were infected with retrovirus expressing RNF10 siRNA, myelin formation was inhibited. These data suggest that RNF10 regulates MAG expression and is required for myelin formation.
Hoshikawa
Shinya
S
Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Ogata
Toru
T
Fujiwara
Sayaka
S
Nakamura
Kozo
K
Tanaka
Sakae
S
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D009186:Myelin Sheath / Q000378:metabolism*; D018992:Myelin-Associated Glycoprotein / Q000235:genetics*; D009474:Neurons / Q000166:cytology; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051381:Rats; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D002352:Carrier Proteins; D018992:Myelin-Associated Glycoprotein; C406487:RNF10 protein, human